(205) Potential Hazardous Effects of Meptyldinocap, a Dinitrophenol Fungicide, on Implantation: Molecular Mechanisms in Porcine Endometrial and Trophectoderm Cells

Wonhyoung Park¹; Sunwoo Park²; Jiyeon Ham³; Whasun Lim⁴; Gwonhwa Song⁵;

1. Department of Animal Science, Chungbuk National University, Cheongju, Republic of Korea

2. Department of GreenBio Science, Gyeongsang National University, Jinju, Republic of Korea

3. Department of Animal Science and Biotechnology, Chungnam National University, Daejeon, Republic of Korea

4. Department of Biological Sciences, Sungkyunkwan University, Suwon, Republic of Korea

5. Department of Biotechnology, Korea University, Seoul, Republic of Korea

Abstract Text:

Meptyldinocap is a powdery mildew fungicide widely used in the cultivation of various crops. It exerts its antifungal effects by uncoupling oxidative phosphorylation in the fungal respiratory process. Given this mechanism of action, we hypothesized that meptyldinocap might also affect mammalian cells, particularly those involved in implantation, an energy-intensive process highly dependent on mitochondrial function. To investigate this, we investigated the effects of meptyldinocap on porcine trophectoderm and endometrial luminal epithelial cells. Our results show that membrane potential of mitochondria has been disrupted by meptyldinocap in both porcine trophectoderm and luminal epithelial cells. In trophectoderm cells, mitochondrial oxygen consumption rate (OCR) measurements revealed a significant reduction in maximal respiration level following exposure to meptyldinocap. Furthermore, a marked increase in GRP78 and p-eIF2α protein expression suggests that meptyldinocap perturbs ER-mitochondria interactions, potentially inducing cellular stress responses.  Notably, we found that mitochondrial impairment induced by meptyldinocap was medicated by calcium ion dysregulation, highlighting a key mechanistic pathway. These results demonstrate that potential harmful effects of meptyldinocap on implantation by focusing mitochondrial function in porcine maternal and fetal cells. This study provides crucial insights into the potential reproductive risks of meptyldinocap in pigs.